Prenatal exposure to persistent and non-persistent chemical mixtures and associations with adverse birth outcomes in the Atlanta African American Maternal-Child Cohort.

BACKGROUND: African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. OBJECTIVE: We examined the individual and mixture effects of non-persistent chemicals and persistent organic pollutants (POPs) on gestational age at birth and birthweight for gestational age z-scores within a prospective cohort of pregnant AAs. METHODS: First-trimester serum and urine samples obtained from participants within the Atlanta African American Maternal-Child cohort were analyzed for 43 environmental chemicals, including per-and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides, pyrethroid insecticides, phthalates, bisphenol A, nicotine, and the primary metabolite of delta-9-tetrahydrocannabinol. Linear regression was used to estimate individual associations between chemicals and gestational age and birthweight z-scores (N ranging from 107 to 523). Mixture associations were estimated using quantile g-computation, principal component (PC) analyses, and hierarchical Bayesian kernel machine regression among complete cases (N = 86). RESULTS: Using quantile g-computation, increasing all chemical exposures by one quantile was modestly associated with a reduction in gestational age (mean change per quartile increase = -0.47, 95% CI = -1.56, 0.61) and birthweight z-scores (mean change per quartile increase = -0.49, 95% CI = -1.14, 0.15). All PCs were associated with a reduction in birthweight z-scores; associations were greatest in magnitude for the two PCs reflecting exposure to combined tobacco, insecticides, PBDEs, and phthalates. In single pollutant models, we observed inconsistent and largely non-significant associations. SIGNIFANCE: We conducted multiple targeted exposure assessment methods to quantify levels of environmental chemicals and leveraged mixture methods to quantify their joint effects on gestational age and birthweight z-scores. Our findings suggest that prenatal exposure to multiple classes of persistent and non-persistent chemicals is associated with reduced gestational age and birthweight z-scores in AAs. IMPACT: African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. In the present study, we analyzed serum and urine samples for levels of 43 environmental chemicals. We used quantile g-computation, principal component analysis, and BKMR to assess associations between chemical exposure mixtures and adverse birth outcomes. Our findings suggest that prenatal exposure to multiple classes of chemicals is associated with reduced birthweight z-scores, a proxy for fetal growth, in AAs.

Per- and polyfluoroalkyl substances and psychosocial stressors have a joint effect on adverse pregnancy outcomes in the Atlanta African American Maternal-Child cohort.

BACKGROUND: African Americans (AAs) experience high rates of adverse pregnancy outcomes relative to Whites. Differential in utero exposure to environmental chemicals and psychosocial stressors may explain some of the observed health disparities, as exposures to per- and polyfluoroalkyl substances (PFAS) and experiences of discrimination have been linked to adverse birth outcomes. Few studies have examined chemicals and non-chemical stressors together as an exposure mixture, which may better reflect real-life exposure patterns. Here, we adapted methods designed for the analysis of exposure mixtures to examine joint effects of PFAS and psychosocial stress on birth outcomes among AAs. METHODS: 348 participants from the Atlanta African American Maternal-Child cohort were included in this study. Four PFAS were measured in first trimester serum samples. Self-report questionnaires were administered during the first trimester and were used to assess psychosocial stress (perceived stress, depression, anxiety, gendered racial stress). Quantile g-computation and Bayesian kernel machine regression (BKMR) were used to estimate the joint effects between PFAS and psychosocial stressors on gestational age at delivery and birthweight for gestational age z-scores. All models were adjusted for maternal education, maternal age, parity, and any alcohol, tobacco and marijuana use. RESULTS: Our analytic sample included a socioeconomically diverse group of pregnant women, with 79 % receiving public health insurance. In quantile g-computation models, a simultaneous one-quartile increase in all PFAS, perceived stress, depression, anxiety, and gendered racial stress was associated with a reduction in birthweight z-scores (mean %change per quartile increase = -0.24, 95 % confidence interval = -0.43, -0.06). BKMR similarly showed that increasing all exposures in the mixture was associated with a modest decrease in birthweight z-scores, but not a reduced length of gestation. DISCUSSION: Using methods designed for analyzing exposure mixtures, we found that a simultaneous increase in in utero PFAS and psychosocial stressors was associated with reduced birthweight for gestational age z-scores.

LC-MS Quantification of Malondialdehyde-Dansylhydrazine Derivatives in Urine and Serum Samples.

We developed a robust analytical method for quantification of malondialdehyde (MDA) in urine and serum samples using dansylhydrazine (DH) as a derivatizing reagent. The derivatization procedure was partially carried out using an autosampler injection program to minimize errors associated with the low-volume addition of reagents and was optimized to yield a stable hydrazone derivative of MDA and its labeled d2-MDA analogue. The target MDA-DH derivatives were separated on an Agilent Zorbax Eclipse Plus Phenyl-Hexyl (3.0 × 100 mm, 3.5 µm) column. The mass-to-charge ratios of the target derivatives [(M+H)+ of 302 and 304 for MDA-DH and d2-MDA-DH, respectively] were analyzed in single ion monitoring mode using a single quadrupole mass spectrometer operated under positive electrospray ionization. The method limits of quantification were 5.63 nM (or 0.405 ng/mL) for urine analysis and 5.68 nM (or 0.409 ng/mL) for serum analysis. The quantification range for urine analysis was 5.63-500 nM (0.405-36.0 ng/mL) while the quantification range for serum analysis was 5.68-341 nM (0.409-24.6 ng/mL). The method showed good relative recoveries (98-103%), good accuracies (92-98%), and acceptable precisions (relative standard deviations 1.8-7.3% for inter-day precision; 1.8-6.1% for intra-day precision) as observed from the repeat analysis of quality control samples prepared at different concentrations. The method was used to measure MDA in individual urine samples (n = 287) and de-identified archived serum samples (n = 22) to assess the overall performance of the method. The results demonstrated that our method is capable of measuring urinary and serum levels of MDA, allowing its future application in epidemiologic investigations.